In summary, our results indicate that TGFBIp is an HtrA1 substrate and that some mutations in the gene encoding TGFBIp cause aberrant HtrA1-mediated processing that results in amyloidogenesis in corneal dystrophies.
Thus, tranilast may be useful in delaying or preventing the recurrence of corneal opacity in TGFBI-linked corneal dystrophies if clinical studies confirm these findings.
There was no significant differences between eyes with betaig-h3R124Hcorneal dystrophy and normal eyes in cell density, coefficient of variation, and cell hexagonality of corneal endothelium.
We review our current understanding of the molecular mechanisms of granular corneal dystrophy type 2 (GCD2) and studies of other TGFBIcorneal dystrophies.
This result indicates the potential of siRNA treatment as a personalized medicine approach for the management of heritable TGFBI-associated corneal dystrophies.
Most of these CDs in the stromal layer of the cornea have been associated with mutations found on the TGFBI gene that codes for a 683-amino acid transforming growth factor induced protein (TGFβIp).
Mutations of the human transforming growth factor beta-induced gene (TGFBI) were reported to cause granular (GCD) and Avellino (ACD) corneal dystrophy in various nationalities.
Three genetic corneal dystrophies [congenital hereditary endothelial dystrophy type 2 (CHED2), Harboyan syndrome and Fuchs endothelial corneal dystrophy] arise from mutations of the SLC4a11 gene, which cause blindness from fluid accumulation in the corneal stroma.
Amyloid and non-amyloid forms of 5q31-linked corneal dystrophy resulting from kerato-epithelin mutations at Arg-124 are associated with abnormal turnover of the protein.
The exclusion of a TGFBI-associated corneal dystrophy in this case, leaving trichiasis as the most likely cause of the corneal amyloid deposition, demonstrates the utility of molecular genetic analysis in confirming or refuting a presumptive clinical diagnosis.
We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation.
Identification of novel mutations, the presence of phenotypic variability, and the genetic heterogeneity seen in our cases stress the need for mandatory screening of TGFBI for precise diagnosis and classification of corneal dystrophies.